Maria Bożentowicz-Wikarek

Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly

Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium–phosphate homoeostasis. The data of recently published studies suggest that FGF‐23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF‐23 (C‐terminal) and iFGF‐23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population.

Are plasma levels of visfatin and retinol-binding protein 4 (RBP4) associated with body mass, metabolic and hormonal disturbances in women with polycystic ovary syndrome?

OBJECTIVE To analyze potential interactions of visfatin and retinol-binding protein 4 (RBP4) levels with body mass, metabolic, and hormonal status in normal weight and obese women with PCOS. STUDY DESIGN Body composition was determined by bioimpedance in 83 women (44 obese) diagnosed with PCOS and in 67 women (36 obese) without PCOS. In addition, serum glucose, lipids, androgens, FSH, LH, SHBG, insulin, visfatin, and RBP4 were measured in a fasting state and the free androgen index (FAI) was calculated, as was insulin resistance using the HOMA-IR assessment. RESULTS Plasma RBP4 levels were significantly higher in women of normal weight compared to obese subjects when both were diagnosed with PCOS (14.1 ± 4.6 vs.10.9 ± 4.5 ng/mL, p<0.001); while in non-PCOS subjects the opposite was found (10.8 ± 4.5 vs. 18.4 ± 11.6 ng/mL, p<0.01; respectively). Plasma visfatin levels were similar in PCOS and non-PCOS subjects. In non-PCOS subjects, positive correlations between RBP4 level and anthropometric parameters were observed. In PCOS, RBP4 levels inversely correlated with serum insulin levels and HOMA-IR values. No correlation was found between plasma visfatin levels and anthropometric parameters in all study groups. Similarly, no correlation was found in PCOS and non-PCOS subgroups. Additionally, there was an inverse correlation between RBP4 and LH concentrations and LH/FSH ratio in all study subjects. CONCLUSIONS Plasma visfatin level is not a useful biomarker of insulin resistance and hyperandrogenism. RBP4 level reflects visceral body fat content in non-PCOS women. Decreasing RBP4 release along with increasing insulin resistance and hormonal disturbances may be a compensatory mechanism preventing deterioration in obese PCOS.

Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population

OBJECTIVE Fibroblast growth factor 23 (FGF23) is a phosphaturic agent involved in calcium-phosphate homeostasis. Recent findings show that iron deficiency and inflammation regulate FGF23 release and/or biodegradation. Iron deficiency is frequently observed in the elderly, therefore the aim of this study was to find out if iron deficiency is independent from low grade inflammatory factors affecting both forms of FGF23 that are detectable in circulation in a large population-based study of elderly subjects. DESIGN AND METHODS The analysis included 3780 elderly (1798 females) PolSenior study participants and assessed levels of phosphorus, calcium, iron, ferritin, interleukin 6, C-reactive protein (hs-CRP), intact (iFGF23), and c-terminal FGF (cFGF23). The analysis was performed for all subjects and terciles of serum iron levels in relation to hs-CRP were calculated. RESULTS The highest plasma cFGF23 and iFGF23 concentrations were found in subjects with the lowest serum iron levels (p<0.001). The effect of low grade inflammation was markedly weaker and affected only iFGF23 levels. The adjusted serum levels of hs-CRP, iPTH, phosphorus, and 25-(OH)-D3 analysis revealed that plasma iFGF23 and cFGF23 levels were almost unchanged up to a serum iron level of 59.3 ng/mL and 57.3 ng/mL respectively and then were nearly linearly increasing by 0.285 pg/mL and 3.742 RU/mL for each unit of serum iron increase. CONCLUSIONS Low iron levels are associated with increased levels of both cFGF23 and iFGF23, independent of low grade inflammation. A similar analysis of cFGF23 and iFGF23 does not suggest enhanced biodegradation of iFGF23 induced by iron deficiency.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy ☆

BACKGROUND Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. MATERIALS AND METHODS Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. RESULTS The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. CONCLUSION Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation.

Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the elderly

BACKGROUND Better biomarkers of CKD reflecting responses to decreased glomerular filtration rate (GFR) are needed. We determined the value of estimated GFR (eGFR) as a threshold for the increase of plasma cFGF23 (C-terminal) and intact fibroblast growth factor-23 (iFGF23) (intact) concentrations in the course of chronic kidney disease (CKD) and compared this eGFR value with values related to increased serum intact parathyroid hormone (iPTH) or phosphorus concentrations in an elderly population. METHODS We measured plasma iFGF23, cFGF23, serum phosphorus, calcium, albumin, creatinine, urea, cystatin C, iPTH and vitamin 25-OH-D3 in 3780 population-based study participants aged ≥ 65 years. RESULTS Serum phosphorus concentrations hardly increased until mean eGFR reached 47.3 ± 4.7 mL/min/1.73 m(2) but then increased exponentially. Similarly, both iPTH and iFGF23 increased slightly in early CKD but then increased exponentially when eGFR reached 55.0 ± 4.2 mL/min/1.73 m(2) for iPTH and 51.6 ± 5.7 mL/min/1.73 m(2) for iFGF23. The departure point for exponential increases in cFGF23 preceded those for iPTH and iFGF23 and occurred at a mean eGFR of 57.7 ± 7.8 mL/min/1.73 m(2). The prevalence of increased iFGF23 occurred at a remarkably higher eGFR value than that of cFGF23 across the CKD stages. CONCLUSIONS The increase in cFGF23 preceded both the increase in iPTH and iFGF23 as eGFR declined. Increased plasma iFGF23 level did not precede the rise in serum iPTH concentrations and did not occur before stage-3 CKD in elderly persons. However, cFGF23 was not an early marker of CKD in the elderly subjects.

The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling.

Abstract Background: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. Materials and methods: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR. Results: The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3 mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for ‘latent inflammation’ proved to be hs-CRP and IL-6 serum levels. In the case of ‘nutritional status’, important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant. Conclusion: The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.

C-Terminal to Intact Fibroblast Growth Factor 23 Ratio in Relation to Estimated Glomerular Filtration Rate in Elderly Population.

Background/Aims: An analytical equivalence between intact fibroblasts growth factor(iFGF23) and C-terminal(cFGF23) assays is logically expected, however, numerous studies demonstrate lack of a strong association between them. Previously, we have demonstrated the increase in cFGF23 slightly precedes the increase of iFGF23 with the impairment of kidney excretory function; without actually analyzing the ratio between both assays, which are postulated to be affected by declining kidney function. Therefore, the aim of this study was to analyze the ratio between C and iFGF23 in relation to the estimated glomerular filtration rate (eGFR) in an elderly population. Methods: We analysed the variability of c/iFGF23 ratio in the population of 3264 elderly PolSenior study participants (≥ 65years) in the relation to eGFR calculated according full Modification of Diet in Renal Disease, serum levels of C-reactive protein (hs-CRP), and iron. Results: The log10(c/i FGF23 ratio) increased in the subsequent CKD stages. Serum iron and CRP levels reduced the log10 and increased it with age in multivariate regression analysis. Conclusions: Our results suggest impairment in the cleavage of the C-terminal FGF23 fragments with the deterioration of kidney excretory function and age in the elderly population. Inflammation and low serum iron level seems to diminish degradation capacity of FGF23 fragments.

Urinary renalase concentration in patients with preserved kidney function undergoing coronary angiography

The purpose of the study was to evaluate urinary renalase concentration before and after coronary angiography/percutaneous coronary interventions (CA/PCI) in patients with coronary artery disease (CAD) and preserved kidney function and verify its potential application as contrast‐induced acute kidney injury (CI‐AKI) diagnostic marker.

Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration is not related to kidney function in elderly subjects.

Abstract Background: Studies assessing plasma visfatin/nicotinamide phosphoribosyltransferase (NAMPT) concentrations in chronic kidney disease with the ELISA method are restricted mainly to subjects with end-stage kidney disease. Therefore, little is known about to what extent glomerular filtration rate (GFR) affects the plasma levels of visfatin/NAMPT. The aim of this study was to assess the relations between circulating visfatin/NAMPT levels and estimated GFR (eGFR), independently of potential confounders such as inflammation, nutritional status, and insulin resistance in the elderly population. Methods: The analysis included 3023 elderly subjects (1076 with impaired kidney excretory function – eGFR <60 mL/min/1.73 m2) who were participants of the PolSenior study. Serum insulin, glucose, creatinine, C-reactive protein, interleukin-6, and plasma visfatin/NAMPT concentrations were measured by a highly specific ELISA method. Insulin resistance was assessed on the basis of homeostasis model assessment for insulin resistance, and kidney excretory function was assessed using the full MDRD formula. Results: Similar plasma visfatin/NAMPT levels were found in subjects with eGFR ≥60 and <60 mL/min/1.73 m2 (0.96 ng/mL in both groups), and even in those subjects with eGFR 15–30 mL/min/1.73 m2 (0.83 ng/mL). Additionally, there was no association between plasma visfatin/NAMPT concentrations and eGFR values in models of regression analysis including confounding factors. Conclusions: The results of our study suggest that plasma visfatin/NAMPT levels are not affected by impaired kidney excretory function in elderly subjects.

Prediction of contrast‐induced acute kidney injury by early post‐procedural analysis of urinary biomarkers and intra‐renal Doppler flow indices in patients undergoing coronary angiography

BACKGROUND The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI). METHODS This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally. RESULTS CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001). CONCLUSIONS Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions.